CYP1A1

Chr 15

cytochrome P450 family 1 subfamily A member 1

Also known as: AHH, CP11, CYP1, CYPIA1, P1-450, P450-C, P450DX

NCBI Gene: 1543 ENSG00000140465 UniProt: P04798

This gene, CYP1A1, encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and its expression is induced by some polycyclic aromatic hydrocarbons (PAHs), some of which are found in cigarette smoke. The enzyme's endogenous substrate is unknown; however, it is able to metabolize some PAHs to carcinogenic intermediates. The gene has been associated with lung cancer risk. A related family member, CYP1A2, is located approximately 25 kb away from CYP1A1 on chromosome 15. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jan 2016]

Research

ResearchGenerating clinical summary…

Active trials

478

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.78

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.78LOEUF

pLI 0.000

Z-score -1.11

OE 1.28 (0.92–1.78)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.36Z-score

OE missense 1.06 (0.96–1.16)

322 obs / 304.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.28 (0.92–1.78)

0≤0.351.4

Missense OE?1.06 (0.96–1.16)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 23 / 17.9Missense obs/exp: 322 / 304.5Syn Z: -0.07

Background carrier burden — how many people carry a rare variant somewhere in CYP1A1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 53

675 rare PASS variants

Rare truncating (LoF)

1 in 600

111 rare PASS variants

Rare synonymous (reference)

1 in 170

293 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CYP1A1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 68	1 in 950
South Asian	~43k	1 in 52	1 in 200
Remaining (unassigned)	~30k	1 in 58	1 in 250
European (Finnish)	~27k	1 in 270	1 in 1,800
Admixed American	~22k	1 in 41	1 in 480
African / African American	~21k	1 in 51	1 in 330
East Asian	~20k	1 in 58	1 in 320
Ashkenazi Jewish	~13k	1 in 210	1 in 570
Middle Eastern	~2,884	1 in 48	1 in 320

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓